Project Summary Microglia are the resident immune cells of the central nervous system and emerging evidence suggests they are influential in shaping the developing brain. Microglia have been proposed to regulate proliferation, differentiation, and neuronal survival in various systems but these studies reveal variable, and often contradictory, functions. Utilizing the simplicity of the embryonic mammalian retina, we can directly assess the role of microglia in regulating neurogenesis. Currently, little is known about microglial function in the developing retina, despite the fact that they infiltrate the neural retina at the onset of neurogenesis and distribute throughout proliferating and newly forming differentiated layers. I have performed preliminary experiments addressing this, and the results suggest that microglia either 1) directly modulate retinal progenitor proliferation and differentiation, or 2) regulate the survival of newly born neurons. Therefore, I will differentiate between these two possibilities, and then identify the signaling pathways involved. Completion of this work will result in the first study of microglial function and phenotype in the developing mammalian retina, and will determine whether microglia are crucial for proper development of the retina. In addition, this proposal will expand on our current understanding of crosstalk between microglia and progenitors/neurons that will shed light on the complex role for these cells in cortical development, adult neurogenesis, and stem cell therapies.